HPV mE7刺激的DCs对宫颈癌小鼠模型的治疗研究  

Therapeutic effect of HPV mE7-stimulated DCs on cervical cancer in mice

作　　者：张战锋[1] 刘媛瑞 徐建华 Zhang Zhanfeng;Liu Yuanrui;Xu Jianhua(Clinical Lab Department,First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405;Clinical Lab Department,Southern Hospital of Southern Medical University,Guangzhou 510515;Laboratory of Oncology Science and Molecular Biology,Shunde Hospital of Guangzhou University of Chinese Medicine,Foshan 528333)

机构地区：[1]广州中医药大学第一附属医院检验科,广州510405 [2]南方医科大学南方医院检验医学部,广州510515 [3]广州中医药大学顺德医院肿瘤与分子生物学实验室,佛山528333

出　　处：《现代妇产科进展》2019年第8期602-605,共4页Progress in Obstetrics and Gynecology

基　　金：创新强院青年科研人才培优项目(No:2015QN08)

摘　　要：目的:研究人乳头瘤病毒(HPV)mE7蛋白刺激后的树突状细胞(DCs)对小鼠体内宫颈癌细胞的杀伤效果。方法:建立宫颈癌细胞TC-1的荷瘤小鼠模型。分离外周血单个核细胞并进行DCs纯化培养,用磷酸盐缓冲液(PBS)、DCs(DCs+PBS)和前期实验表达纯化的HPVmE7蛋白刺激的DCs(DCs+HPVmE7)分别对荷瘤小鼠进行细胞免疫,观察小鼠体内肿瘤生长并检测小鼠脾细胞对TC-1细胞的体外裂解率、IFN-γ及血清中IL-12表达水平。结果:植入小鼠皮下的TC-1细胞具有典型的肿瘤细胞特征。DCs+PBS组和DCs+HPVmE7组中脾细胞对TC-1细胞的体外裂解率及IFN-γ表达水平均高于PBS组(P<0.01),DCs+HPVmE7组高于DCs+PBS组(P<0.01);DCs+PBS组和DCs+HPVmE7组中IL-12表达水平高于PBS组(P<0.01),前两组比较无显著差异(P>0.05)。随着时间延长,小鼠体内的肿瘤体积逐渐增大,DCs+PBS组和DCs+HPVmE7组的肿瘤体积增长速度明显降低(从第12天开始,DCs组与PBS组比较均P<0.01),DCs+PBS组和DCs+HPVmE7组的肿瘤增长速度无显著差异(P>0.05)。结论:成功构建宫颈癌细胞TC-1的荷瘤小鼠模型。DCs对TC-1细胞瘤体的生长具有一定的抑制作用,但特异性抗原的刺激对促进DCs杀伤肿瘤细胞的作用有限。Objective:To study the killing effect of DCs stimulated by HPV mE7 protein on cervical cancer cells in mice. Methods:The tumor-bearing mice model of cervical cancer cell line TC-1 was established.Peripheral blood mononuclear cells (PBMCs) were isolated and cultured for DCs purification.The tumor-bearing mice were immunized with DCs (HPV mE7 stimulated),PBS and DCs(PBS) respectively.The growth of tumor in vivo was observed.The disruption rate of mouse spleen cells to TC-1 cells cultured in vitro and the levels of IFN-γ and IL-12 were measured. Results:The TC-1 cells implanted under the skin of mice showed typical tumor cell characteristics.The disruption rate and the expression level of IFN-γ were highest in DCs(HPV mE7) group and lowest in PBS group( P <0.01).The expression of IL-12 in DCs PBS group and DCs HPV mE7 group was higher than that in PBS group( P <0.01),but there was no significant difference between the first two groups ( P >0.05).With the prolongation of time,the tumor volume of the mice increased gradually.But the growth rate of tumor volume reduced in DCs (PBS) and DCs (HPV mE7) groups.There was no significant difference in tumor growth rate between DCs PBS group and DCs HPV mE7 group P >0.05). Conclusions:The tumor-bearing mice model of cervical cancer cell line TC-1 was successfully constructed,and DCs could inhibit the growth of TC-1 cells to a certain extent.But the stimulation of HPVm E7 had limited effect on promoting the killing effect of DCs.

关 键 词：宫颈癌 免疫治疗 人乳头瘤状病毒 

分 类 号：R737.33[医药卫生—肿瘤]